SPECIAL SECTION SPECIAL SECTIONS EDITOR: JOHN E. SCHOWALTER, M.D.
GENETICS AND CHILD PSYCHIATRY GUEST EDITORS: JAMES F. LECKMAN, M.D.,
AND
DAVID L. PAULS, PH.D.
Introduction 1984). If these findings are replicated, it may be useful to examine the pattern of vertical transmission seen in these families in an effort to determine what mode of transmission best approximates the observed data (Price et al., 1987). The third report provides limited empirical support to the view that minor physical anomalies and attention deficit hyperactivity disorder may represent independent expressions of a single underlying trait that is transmissible within affected families (Deutsch et aI., 1990). The report is noteworthy because of the use of latent structure analysis (16reskog and Sorbom, 1976) in evaluating the results. This technique may prove useful in evaluating other data, particularly when longitudinal data are combined with other analytic procedures such as segregation analysis. To some extent, each of these initial three reports must be viewed as preliminary because of their small sample sizes and their reliance, to a greater or lesser degree, on family history methods to obtain information concerning affected relatives. This technique tends to underestimate the number of affected relatives and provides a less complete picture of the individual family member than a study that includes a direct interview (Orvaschel et aI., 1982). Genetic studies in psychiatry have become increasingly fashionable during the past decade (Vandenberg et aI., 1986; Leckman et aI., 1987). This enthusiasm is due in part to the revolutionary advances that have been made in the field of molecular genetics and our ability to localize and characterise abnormal genes. The use ofrecombinant DNA techniques to map the human genome and to perform genetic linkage studies in large extended families in order to determine the chromosomal localization of abnormal genes has had an enormous impact. Well-known examples include the localization of some of the genes responsible for Huntington's chorea (Gusella et aI., 1983), bipolar affective disorder (Egeland et aI., 1987; Baron et aI., 1987), and schizophrenia (Sherrington et aI., 1988). Although controversy surrounds some of these reports (Kelsoe et aI., 1989; Kennedy et al., 1989), the promise of genetic linkage studies is undiminished. Two of the studies in this special section document progress that is currently being made with regard to Tourette's syndrome and some forms of familial dyslexia. Pauls et al. (1990) report on efforts to localize the gene for Tourette' s
The articles in this special section of the Journal illustrate some of the approaches used to investigate the role of genetic factors in establishing the constitutional vulnerabilities associated with mental, behavioral, and developmental disorders of childhood onset. The reports focus on disorders for which genetic factors have either been convincingly demonstrated such as fragile-X syndrome, some forms of dyslexia, and Tourette 's syndrome, or where there is strong presumptive evidence, as in childhood affective disorders, attention deficit hyperactivity disorder, and autism. Three of the studies focus on efforts to define better the range of phenotypic expression (clinical presentations) associated with certain disorders. Piven et al. (1990) examine the range of abnormal phenotypes seen in the siblings of adult autistic subjects in an effort to define the "lesser variants" of this syndrome. The report builds on the important work of Folstein and Rutter (1977) which provided a clear indication that genetic factors contribute to the development of autism and that lesser variants such as severe social dysfunction and cognitive impairments may be present in close family members. Historically, this report is also of special interest as it contains information concerning that sample of autistic subjects initially described by Kanner (1943) in his classic description of this syndrome. The report of Orvaschel (1990) focuses on children at high risk of developing an affective disorder and reminds us again of the etiological heterogeneity that underlies mood disorders. The study lends further evidence that some forms of recurrent affective disorder are associated with very early onset and are often present with a prominant admixture of anxiety symptoms (Leckman et aI., 1983; Weissman et aI.,
Accepted September 21. 1989. From the Child Study Center, the Children's Clinical Research Center, and the Departments of Human Genetics, Psychiatry and Pediatrics, Yale University School ofMedicine , New Haven, Connecticut. This work was supported in part by federal grants: RR00125 , HD03008, MH03029 , MH00508, and NS16648; and by supportfrom the Tourette's Syndrome Association and the John Merck Fund. Reprint requests to Dr. Leckman, 1-269 SHM. Child Study Center, Yale University School of Medicine, P.O. Box 3333, New Haven, CT 06510. 0890-8567/90/2902-0 I74$02.00/0© 1990 by the American Academy of Child and Adolescent Psychiatry.
174
GENETICS: INTRODUCTION
syndrome in several large multigenerational families. The report describes the current status of the search for the putative gene and documents that over a third of the human genome has been examined. It also reminds us that linkage studies are not trivial undertakings. They are costly and methodologically demanding, so that the threshold for embarking on such studies should be high and should include preliminary evidence that a single major gene may be involved in the transmission of the disorder has has been demonstrated in Tourette 's syndrome (Pauls and Leckman, 1986). The study of Smith and colleagues (1990) provides an update on the reported linkage of some forms of familial dyslexia to cytogenetic markers on chromosome 15 (Smith et al., 1983). The report demonstrates that there is genetic heterogeneity (different genetic mutations lead to the same clinical outcome) for this disorder. In the short term, genetic linkage studies will improve diagnostic procedures, permit more accurate genetic counseling, and facilitate more precise longitudinal studies of genetically vulnerable individuals. This potential is amply demonstrated in the report of Hodapp et al. (1990) in which individuals with fragile X syndrome tend to have a similar trajectory with regard to cognitive development. This is an example of how knowledge of genetic factors can be used to define an etiologically homogenous population so that more precise longitudinal studies can be performed. Eventually such strategies can be used in conjunction with intervention studies or studies of specific risk or protective factors in order to identify the biological mechanisms that underlie this unusual course for cognitive development and to devise intervention programs that take these factors into account. The final report in this special section exemplifies efforts to define the risk and protective factors associated with the development of a genetically mediated disorder (Leckman et aI., 1990). It emphasizes the apparent role of perinatal factors in mediating the severity of tic disorder in childhood. As such it sets the stage and emphasizes the need for etiological models that can be empirically tested for prospective longitudinal studies of children at risk for Tourette 's syndrome. Ideally, such a study would be performed in conjunction with linked chromosomal markers so that the effect of putative risk or protective factors could be evaluated in an etiologically homogenous group. Several of the articles in this special section remind us of other scientific gains that have contributed to progress in this field including: uniform diagnostic criteria such as DSMIII-R, structured diagnostic interview schedules, and specialized research designs and analytic techniques (Orvaschel, 1990; Pauls et al., 1990; Leckman et al., 1990). They also serve to remind us of the challenges that confront investigators interested in better understanding the role of genetic factors. These include the range of variation seen in normal development and the complex natural history of these disorders. For example, some symptoms such as motoric hyperactivity, impulsivity, tics, and some forms of reading disability may improve over the course of development, so that if an individual with a childhood history of J .Am.Acad. Child Adolesc. Psychiatry, 29:2, March 1990
one of these difficulties was evaluated as an adult, his/her current functioning may not accurately reflect earlier problems. On the other hand, retrospective reporting is also prone to error. Questions concerning the continuity or discontinuity of symptoms and disorder are amenable to prospective longitudinal studies. However, the ideal longitudinal study would focus on an etiologically homogenous population. This special section does not include examples of twin studies or adoption studies, although they have frequently provided the best initial indication that a particular trait or disorder is determined in part by genetic factors; nor does it provide examples of molecular genetic studies that will need to take place in order to characterize the abnormal genes responsible for an individual's vulnerability to a particular disorder. Molecular genetics and the developmental neurosciences are among the basic research disciplines that underlie child psychiatry. These fields are in the midst of an enormous expansion fueled by technical advances that have placed virtually every genetic message within our grasp. Progress in these fields will have a dramatic impact on our understanding of eNS development and the elaborate interplay of biological potentialities and environmental experiences that determines its course and defines our individuality. This in tum will lead to a much more complete understanding of the pathophysiology of these conditions and, hopefully, will provide insights that can be translated into the development of early intervention programs for vulnerable individuals and improved treatment for individuals already affected.
References Baron, M., Risch, N., Hamburger, R. et al. (1987), Genetic linkage between X-chromosome markers and bipolar affective illness. Nature, 326:289-292. Deutsch, C. K., Matthysse, S., Swanson, J. M. & Farkas, L. G. (1990), Genetic latent structure analysis of dysmorphology in attention deficit disorder. J. Am. Acad. Child Adolesc. Psychiatry. 29:189-194. Egeland, J. A., Gerhard, D. S., Pauls, D. L., et al. (1987), Bipolar affective disorders linked to DNA markers on chromosome II. Nature, 325:783-787. Folstein, S. & Rutter, M. (1977), Infantile autism: a genetic study of 21 twin pairs. J. Child Psychol. Psychiatry, 18:297-321. Gusella, J. F., Wexler, N. S., Conneally, P. M. et al. (1983), A polymorphic DNA marker genetically linked to Huntington's disease. Nature, 306:234-239. Hodapp, R. M., Dykens, E. M., Hagerman, R. et al. (1990), Developmental implications of changing trajectories of IQ in males with fragile X syndrome. J. Am. Acad. Child Adolesc. Psychiatry, 29:214-219. Joreskog, K. G. & Sorbom, D. (1976), Statistical models and methods for test-retest situations. In: Advances in Psychological and Educational Measurement, eds. D. N. M. de Gruijter, L. J. T. van der Karnp, & J. F. Crombag. London: Wiley. Kanner, L. (1943), Autistic disturbances of affective contact. Nervous Child, 2:217-250. Kelsoe, J., Ginns , E. I., Egeland, J. A., et al. (1989), Reevaluation of the linkage relationship between chromosome II p loci and the gene for bipolar affective disorder in the Old Order Amish. Nature, 342:238-243. Kennedy, J. L., Giuffra, L. A., Moises, H. W., et al. (1989), Molecular genetic studies in schizophrenia. Schizophr. Bull., 15:383391. Leckrnan, J. F., Dolnansky, E. S., Hardin, M. T., et al. (1990),
175
LECKM AN AND PA ULS
Perinatal factor s in the expressio n of Tourettes syndro me: an exploratory study . l . Am. Acad . Child Adolesc . Psychiatry , 29:22G226 . - - Weissman, M. M ., Merikangas. K. R. . Pauls . D . L. & Prusoff. B. A. (1983 ), Panic disorder and major depres sion . Arch . Gen. Psychiatry , 40:1055-1060 . - - - - Pauls , D. L. & Kidd , K. K . (1987), Family-genetic studies and identification of valid diagnostic cate gories in adult and child psychiatry. Br . l . Psychiatry. 5 1:39-44 . Orvashel, H . (1990 ), Early onse t psychiatri c disorder in high risk children and increased fam ilial morb idity of depre ssion and anxiety in their second degree relatives . l . Am . Acad . Child Adolesc . Psychiatry. 29:184- 188. --Thompson, W . D. , Belanger A. , Prusoff, B. A. & Kidd , K. K. ( 1982), Comparison of the family histor y method to direct intervie w factors affecting the diagn osis of depre ssion. l . Affect. Disord . 4:4959. Pauls, D . L. & Leckman , J. F. (1986), The inheritance of Gilles de la Tourette's syndrome and associ ated behaviors: eviden ce for autosomal dominant transmi ssion . N . Engl. l. Med .. 315:993-997 . - - Kurian, R., Kidd, K. K. et al. (1990), Segregation and linkage analyses of Gilles de la Tourette' s syndrome and related disorders . l. Am. Acad. Child Adolesc . Psychiatry , 29: 195-203.
176
Piven , 1., Gayle , J. , Chase , G . , et al. (1990), A family history study of neurop sych iatric disorders in the adult siblings of autist ic ind ividuals. l . Am . Acad . Child Adolesc. Psychiatry. 29:177- 183. Price. R. A., Kidd , K. K. & Weiss man, M. M . ( 1987), Early onset (under age 30 years) and panic disorder as markers for etiologic homogeneity in major depressio n . Arch . Gen . Psychiatry, 44:434440. Sherrington, R. , Brynjolfsson , J., Petursson , H . et al. (1988), Localization of a susceptibility locus for schiyo phrenia on ch romosome 5. Nature. 336:164- 167 . Smith, S. D. , Kimberling, W. J., Penn ington , B. F. & Lub s, H . A. (1983), Specific read ing d isability: identification of an inherited form through linkage analysis . Scie nce. 2 19: 1345-1 347 . - - Pennington . B. F.. Kimberl ing, W . J . & lng, P. S . (1990), Familial dyslexi a: use of genet ic linkage data to def ine subtypes . J , Am. Acad. Child Adolesc. Psychiatry . 29:204-21 3. Vandenberg, S. G . , Singer , S. M. & Pauls, D. L. (1986 ), The Heredity of Behavior Disorders in Adults with Children. New York : Plenum Medical Book Co . Weissman, M. M., Leckm an , J. F., Merikangas, K. R. & Gammon . G. D. (1984) Depression and anxiety in children (age s 6-17 ) of parents with depressi on and anxiety disorders . Arch . Gen . Psychiatry. 41 :845-852.
l.Am.Acad. Child Adolesc.Psychiatry , 29:2, March 1990
GENETICS AND CHILD PSYCHIATRY GUEST EDITORS: JAMES F. LECKMAN, M.D.,
AND
DAVID L. PAULS, PH.D.
Introduction 1984). If these findings are replicated, it may be useful to examine the pattern of vertical transmission seen in these families in an effort to determine what mode of transmission best approximates the observed data (Price et al., 1987). The third report provides limited empirical support to the view that minor physical anomalies and attention deficit hyperactivity disorder may represent independent expressions of a single underlying trait that is transmissible within affected families (Deutsch et aI., 1990). The report is noteworthy because of the use of latent structure analysis (16reskog and Sorbom, 1976) in evaluating the results. This technique may prove useful in evaluating other data, particularly when longitudinal data are combined with other analytic procedures such as segregation analysis. To some extent, each of these initial three reports must be viewed as preliminary because of their small sample sizes and their reliance, to a greater or lesser degree, on family history methods to obtain information concerning affected relatives. This technique tends to underestimate the number of affected relatives and provides a less complete picture of the individual family member than a study that includes a direct interview (Orvaschel et aI., 1982). Genetic studies in psychiatry have become increasingly fashionable during the past decade (Vandenberg et aI., 1986; Leckman et aI., 1987). This enthusiasm is due in part to the revolutionary advances that have been made in the field of molecular genetics and our ability to localize and characterise abnormal genes. The use ofrecombinant DNA techniques to map the human genome and to perform genetic linkage studies in large extended families in order to determine the chromosomal localization of abnormal genes has had an enormous impact. Well-known examples include the localization of some of the genes responsible for Huntington's chorea (Gusella et aI., 1983), bipolar affective disorder (Egeland et aI., 1987; Baron et aI., 1987), and schizophrenia (Sherrington et aI., 1988). Although controversy surrounds some of these reports (Kelsoe et aI., 1989; Kennedy et al., 1989), the promise of genetic linkage studies is undiminished. Two of the studies in this special section document progress that is currently being made with regard to Tourette's syndrome and some forms of familial dyslexia. Pauls et al. (1990) report on efforts to localize the gene for Tourette' s
The articles in this special section of the Journal illustrate some of the approaches used to investigate the role of genetic factors in establishing the constitutional vulnerabilities associated with mental, behavioral, and developmental disorders of childhood onset. The reports focus on disorders for which genetic factors have either been convincingly demonstrated such as fragile-X syndrome, some forms of dyslexia, and Tourette 's syndrome, or where there is strong presumptive evidence, as in childhood affective disorders, attention deficit hyperactivity disorder, and autism. Three of the studies focus on efforts to define better the range of phenotypic expression (clinical presentations) associated with certain disorders. Piven et al. (1990) examine the range of abnormal phenotypes seen in the siblings of adult autistic subjects in an effort to define the "lesser variants" of this syndrome. The report builds on the important work of Folstein and Rutter (1977) which provided a clear indication that genetic factors contribute to the development of autism and that lesser variants such as severe social dysfunction and cognitive impairments may be present in close family members. Historically, this report is also of special interest as it contains information concerning that sample of autistic subjects initially described by Kanner (1943) in his classic description of this syndrome. The report of Orvaschel (1990) focuses on children at high risk of developing an affective disorder and reminds us again of the etiological heterogeneity that underlies mood disorders. The study lends further evidence that some forms of recurrent affective disorder are associated with very early onset and are often present with a prominant admixture of anxiety symptoms (Leckman et aI., 1983; Weissman et aI.,
Accepted September 21. 1989. From the Child Study Center, the Children's Clinical Research Center, and the Departments of Human Genetics, Psychiatry and Pediatrics, Yale University School ofMedicine , New Haven, Connecticut. This work was supported in part by federal grants: RR00125 , HD03008, MH03029 , MH00508, and NS16648; and by supportfrom the Tourette's Syndrome Association and the John Merck Fund. Reprint requests to Dr. Leckman, 1-269 SHM. Child Study Center, Yale University School of Medicine, P.O. Box 3333, New Haven, CT 06510. 0890-8567/90/2902-0 I74$02.00/0© 1990 by the American Academy of Child and Adolescent Psychiatry.
174
GENETICS: INTRODUCTION
syndrome in several large multigenerational families. The report describes the current status of the search for the putative gene and documents that over a third of the human genome has been examined. It also reminds us that linkage studies are not trivial undertakings. They are costly and methodologically demanding, so that the threshold for embarking on such studies should be high and should include preliminary evidence that a single major gene may be involved in the transmission of the disorder has has been demonstrated in Tourette 's syndrome (Pauls and Leckman, 1986). The study of Smith and colleagues (1990) provides an update on the reported linkage of some forms of familial dyslexia to cytogenetic markers on chromosome 15 (Smith et al., 1983). The report demonstrates that there is genetic heterogeneity (different genetic mutations lead to the same clinical outcome) for this disorder. In the short term, genetic linkage studies will improve diagnostic procedures, permit more accurate genetic counseling, and facilitate more precise longitudinal studies of genetically vulnerable individuals. This potential is amply demonstrated in the report of Hodapp et al. (1990) in which individuals with fragile X syndrome tend to have a similar trajectory with regard to cognitive development. This is an example of how knowledge of genetic factors can be used to define an etiologically homogenous population so that more precise longitudinal studies can be performed. Eventually such strategies can be used in conjunction with intervention studies or studies of specific risk or protective factors in order to identify the biological mechanisms that underlie this unusual course for cognitive development and to devise intervention programs that take these factors into account. The final report in this special section exemplifies efforts to define the risk and protective factors associated with the development of a genetically mediated disorder (Leckman et aI., 1990). It emphasizes the apparent role of perinatal factors in mediating the severity of tic disorder in childhood. As such it sets the stage and emphasizes the need for etiological models that can be empirically tested for prospective longitudinal studies of children at risk for Tourette 's syndrome. Ideally, such a study would be performed in conjunction with linked chromosomal markers so that the effect of putative risk or protective factors could be evaluated in an etiologically homogenous group. Several of the articles in this special section remind us of other scientific gains that have contributed to progress in this field including: uniform diagnostic criteria such as DSMIII-R, structured diagnostic interview schedules, and specialized research designs and analytic techniques (Orvaschel, 1990; Pauls et al., 1990; Leckman et al., 1990). They also serve to remind us of the challenges that confront investigators interested in better understanding the role of genetic factors. These include the range of variation seen in normal development and the complex natural history of these disorders. For example, some symptoms such as motoric hyperactivity, impulsivity, tics, and some forms of reading disability may improve over the course of development, so that if an individual with a childhood history of J .Am.Acad. Child Adolesc. Psychiatry, 29:2, March 1990
one of these difficulties was evaluated as an adult, his/her current functioning may not accurately reflect earlier problems. On the other hand, retrospective reporting is also prone to error. Questions concerning the continuity or discontinuity of symptoms and disorder are amenable to prospective longitudinal studies. However, the ideal longitudinal study would focus on an etiologically homogenous population. This special section does not include examples of twin studies or adoption studies, although they have frequently provided the best initial indication that a particular trait or disorder is determined in part by genetic factors; nor does it provide examples of molecular genetic studies that will need to take place in order to characterize the abnormal genes responsible for an individual's vulnerability to a particular disorder. Molecular genetics and the developmental neurosciences are among the basic research disciplines that underlie child psychiatry. These fields are in the midst of an enormous expansion fueled by technical advances that have placed virtually every genetic message within our grasp. Progress in these fields will have a dramatic impact on our understanding of eNS development and the elaborate interplay of biological potentialities and environmental experiences that determines its course and defines our individuality. This in tum will lead to a much more complete understanding of the pathophysiology of these conditions and, hopefully, will provide insights that can be translated into the development of early intervention programs for vulnerable individuals and improved treatment for individuals already affected.
References Baron, M., Risch, N., Hamburger, R. et al. (1987), Genetic linkage between X-chromosome markers and bipolar affective illness. Nature, 326:289-292. Deutsch, C. K., Matthysse, S., Swanson, J. M. & Farkas, L. G. (1990), Genetic latent structure analysis of dysmorphology in attention deficit disorder. J. Am. Acad. Child Adolesc. Psychiatry. 29:189-194. Egeland, J. A., Gerhard, D. S., Pauls, D. L., et al. (1987), Bipolar affective disorders linked to DNA markers on chromosome II. Nature, 325:783-787. Folstein, S. & Rutter, M. (1977), Infantile autism: a genetic study of 21 twin pairs. J. Child Psychol. Psychiatry, 18:297-321. Gusella, J. F., Wexler, N. S., Conneally, P. M. et al. (1983), A polymorphic DNA marker genetically linked to Huntington's disease. Nature, 306:234-239. Hodapp, R. M., Dykens, E. M., Hagerman, R. et al. (1990), Developmental implications of changing trajectories of IQ in males with fragile X syndrome. J. Am. Acad. Child Adolesc. Psychiatry, 29:214-219. Joreskog, K. G. & Sorbom, D. (1976), Statistical models and methods for test-retest situations. In: Advances in Psychological and Educational Measurement, eds. D. N. M. de Gruijter, L. J. T. van der Karnp, & J. F. Crombag. London: Wiley. Kanner, L. (1943), Autistic disturbances of affective contact. Nervous Child, 2:217-250. Kelsoe, J., Ginns , E. I., Egeland, J. A., et al. (1989), Reevaluation of the linkage relationship between chromosome II p loci and the gene for bipolar affective disorder in the Old Order Amish. Nature, 342:238-243. Kennedy, J. L., Giuffra, L. A., Moises, H. W., et al. (1989), Molecular genetic studies in schizophrenia. Schizophr. Bull., 15:383391. Leckrnan, J. F., Dolnansky, E. S., Hardin, M. T., et al. (1990),
175
LECKM AN AND PA ULS
Perinatal factor s in the expressio n of Tourettes syndro me: an exploratory study . l . Am. Acad . Child Adolesc . Psychiatry , 29:22G226 . - - Weissman, M. M ., Merikangas. K. R. . Pauls . D . L. & Prusoff. B. A. (1983 ), Panic disorder and major depres sion . Arch . Gen. Psychiatry , 40:1055-1060 . - - - - Pauls , D. L. & Kidd , K. K . (1987), Family-genetic studies and identification of valid diagnostic cate gories in adult and child psychiatry. Br . l . Psychiatry. 5 1:39-44 . Orvashel, H . (1990 ), Early onse t psychiatri c disorder in high risk children and increased fam ilial morb idity of depre ssion and anxiety in their second degree relatives . l . Am . Acad . Child Adolesc . Psychiatry. 29:184- 188. --Thompson, W . D. , Belanger A. , Prusoff, B. A. & Kidd , K. K. ( 1982), Comparison of the family histor y method to direct intervie w factors affecting the diagn osis of depre ssion. l . Affect. Disord . 4:4959. Pauls, D . L. & Leckman , J. F. (1986), The inheritance of Gilles de la Tourette's syndrome and associ ated behaviors: eviden ce for autosomal dominant transmi ssion . N . Engl. l. Med .. 315:993-997 . - - Kurian, R., Kidd, K. K. et al. (1990), Segregation and linkage analyses of Gilles de la Tourette' s syndrome and related disorders . l. Am. Acad. Child Adolesc . Psychiatry , 29: 195-203.
176
Piven , 1., Gayle , J. , Chase , G . , et al. (1990), A family history study of neurop sych iatric disorders in the adult siblings of autist ic ind ividuals. l . Am . Acad . Child Adolesc. Psychiatry. 29:177- 183. Price. R. A., Kidd , K. K. & Weiss man, M. M . ( 1987), Early onset (under age 30 years) and panic disorder as markers for etiologic homogeneity in major depressio n . Arch . Gen . Psychiatry, 44:434440. Sherrington, R. , Brynjolfsson , J., Petursson , H . et al. (1988), Localization of a susceptibility locus for schiyo phrenia on ch romosome 5. Nature. 336:164- 167 . Smith, S. D. , Kimberling, W. J., Penn ington , B. F. & Lub s, H . A. (1983), Specific read ing d isability: identification of an inherited form through linkage analysis . Scie nce. 2 19: 1345-1 347 . - - Pennington . B. F.. Kimberl ing, W . J . & lng, P. S . (1990), Familial dyslexi a: use of genet ic linkage data to def ine subtypes . J , Am. Acad. Child Adolesc. Psychiatry . 29:204-21 3. Vandenberg, S. G . , Singer , S. M. & Pauls, D. L. (1986 ), The Heredity of Behavior Disorders in Adults with Children. New York : Plenum Medical Book Co . Weissman, M. M., Leckm an , J. F., Merikangas, K. R. & Gammon . G. D. (1984) Depression and anxiety in children (age s 6-17 ) of parents with depressi on and anxiety disorders . Arch . Gen . Psychiatry. 41 :845-852.
l.Am.Acad. Child Adolesc.Psychiatry , 29:2, March 1990
